Using Microfluidics to Make Microdroplets Containing Single Molecules of Interest

Published on September 22, 2009 at 7:51 PM

Inventing a useful new tool for creating chemical reactions between single
molecules, scientists at the National
Institute of Standards and Technology (NIST) have employed microfluidics-the
manipulation of fluids at the microscopic scale-to make microdroplets that contain
single molecules of interest. By combining this new microfluidic "droplet-on-demand"
method with "optical tweezers" that could merge multiple droplets and cause
their molecular contents to react, the research may ultimately lead to a compact,
integrated setup for obtaining single-molecule information on the structure
and function of important organic materials, such as proteins, enzymes, and
DNA.

The NIST "on-demand" single-molecule drop dispenser: Water flows through a microfluidic channel, roughly 35 microns wide, and enters a narrow constriction where it breaks up into droplets. Varying the width of the constriction changes the size of the drops and lacing the water with desired molecules of just the right concentration causes the resulting droplets to pick up single molecules of interest 99 percent of the time. Credit: C. López-Mariscal and K. Helmerson, NIST

With the aid of NIST’s Center for Nanoscale Science and Technology, physicists
Carlos López-Mariscal and Kristian Helmerson created a tiny microfluidic
device with a channel through which water can flow. Squeezed into a narrow stream
by a mixture of oils whose viscosity, or resistance to flow, exerts pressure
on it, the water then enters a narrow constriction. The water’s abrupt
pressure drop-accompanied by a dash of detergent-breaks its surface
tension, splitting it into small droplets. (This same effect occurs when a thin
stream of water falling from a faucet breaks up into small drops.)

The droplet sizes are highly uniform and can be tuned by adjusting the width
of the constriction. With this technique, the researchers made droplets about
a micrometer in diameter-or half an attoliter (half a billionth of a billionth
of a liter) in volume.

In the microfluidic channel, the water is laced with desired molecules of just
the right concentration, so that resulting droplets each pick up on average
just one molecule of interest. Inside each droplet, the individual molecules
of interest slosh around freely in the relatively roomy sphere, along with the
water molecules that make up the bulk of every droplet.

By using laser beams, the researchers can move two or more single-molecule-containing
droplets, cause them to coalesce, and observe the reactions through optical
methods. For their initial reactions, the researchers are mixing fluorescent
molecules that emit different colors, but in the future, they envision more
interesting chemical reactions, such as those between an infectious agent and
an antibody, or a chromosome and a drug. The researchers can shape a laser beam
into any desired pattern and thereby trap not only single drops, but arrays
of them, opening up new possibilities for single-molecule spectroscopy.